12-112405916-G-C

Variant names:

• chr12-112405916-G-C
• rs369557690
• NM_000970.6:c.651C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000970.6(RPL6):​c.651C>G​(p.Phe217Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPL6 NM_000970.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 1 publications found

Genes affected

RPL6 (HGNC:10362): (ribosomal protein L6) This gene encodes a protein component of the 60S ribosomal subunit. This protein can bind specifically to domain C of the tax-responsive enhancer element of human T-cell leukemia virus type 1, and may participate in tax-mediated transactivation of transcription. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed throughout the genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ENSG00000305485 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.876

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000970.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL6	NM_000970.6	MANE Select	c.651C>G	p.Phe217Leu	missense	Exon 6 of 7	NP_000961.2
	RPL6	NM_001024662.3		c.651C>G	p.Phe217Leu	missense	Exon 6 of 7	NP_001019833.1	Q02878
	RPL6	NM_001320137.2		c.651C>G	p.Phe217Leu	missense	Exon 6 of 7	NP_001307066.1	Q02878

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPL6	ENST00000202773.14	TSL:1 MANE Select	c.651C>G	p.Phe217Leu	missense	Exon 6 of 7	ENSP00000202773.9	Q02878
	RPL6	ENST00000424576.6	TSL:1	c.651C>G	p.Phe217Leu	missense	Exon 6 of 7	ENSP00000403172.2	Q02878
	RPL6	ENST00000935343.1		c.729C>G	p.Phe243Leu	missense	Exon 6 of 7	ENSP00000605402.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Benign	0.058
Eigen_PC	Benign	0.0038
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.1
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-4.4	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.047	D
Polyphen		0.71	P
Vest4		0.75
MutPred		0.75		Loss of methylation at K218 (P = 0.0317)
MVP		0.74
MPC		1.9
ClinPred		0.99	D
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.70
Mutation Taster		=24/76	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs369557690; hg19: chr12-112843720; COSMIC: COSV52516814; COSMIC: COSV52516814;